Compounds having a β-amino acid site such as 3-phenylisoserine derivatives are known to be compounds that are industrially useful for pharmaceuticals and the like. Known examples of methods of producing a 3-phenylisoserine derivative include the following:
(1) a method in which methyl phenylglycidate is subjected to a ring-opening reaction with hydrogen azide in the presence of boron trifluoride, and the resulting azide is subjected to benzoylation and catalytic hydrogenation to produce N-benzoyl-3-phenylisoserine methyl ester (see WO 1993/010076);
(2) a method in which 3-phenylisoserine is esterified in methanol, and benzoyl chloride is reacted with its concentrate in water to produce N-benzoyl-3-phenylisoserine methyl ester (see WO 1997/002236); and
(3) a method in which 3-phenylisoserine is reacted with benzoyl chloride in water, and the pH of the reaction liquid is changed to an acidic pH to allow precipitation of a crystalline product, followed by isolation of the product by solid-liquid separation to obtain N-benzoyl-3-phenylisoserine (see The Journal of Organic Chemistry (1992), 57(15) 4320-4323).
However, in method (1), use of a highly toxic material and a highly explosive azide intermediate is required, which is industrially problematic.
Method (2) is a production method in which esterification is followed by protection of an amino group. In method (2), 3-phenylisoserine methyl ester is obtained as an intermediate by carrying out the esterification in advance. However, since the intermediate has a free amino group and an ester moiety in the molecule, by-production of an intermolecular or intramolecular amide body may occur during the subsequent reaction for protection of the amino group. Moreover, in general, methyl ester bodies easily cause hydrolysis at the same time, resulting in poor quality and a low yield.
In method (3), N-benzoyl-3-phenylisoserine ester can be obtained by esterification of the crystals isolated by the solid-liquid separation. Since crystals precipitated by acid precipitation are generally very fine, the method has problems from the viewpoint of industrial production such as a requirement of a very long time for the solid-liquid separation and a high liquid-containing rate of the crystals.
It could therefore be helpful to provide an industrially suitable method of producing a 3-phenylisoserine derivative, which is important as a material for pharmaceuticals and the like.